Post-COVID Cough Linked to Neurological Dysfunction

Chronic cough remains a common reason for consultation in pulmonology post–COVID-19. But what do we really know about this condition, now 5 years after the pandemic’s onset? This topic was discussed at the recent French-Speaking Pneumology Congress held in Marseille, France, from January 24-26, 2025.

Before discussing post-COVID cough, it is crucial to differentiate between an acute cough, often viral in origin (including those associated with SARS-CoV-2), a subacute cough (lasting 3-8 weeks), and a chronic cough (persisting over 8 weeks).

“This distinction allows us to tailor treatment and prescribe the appropriate investigations, according to the duration and the probability of symptom resolution,” explained Laurent Guilleminault, MD, PhD, pulmonologist at Toulouse University Hospital Centre, Toulouse, France.

In the case of an acute cough, for instance, after a viral infection, the probability of spontaneous resolution is very high. It is often unnecessary to carry out additional examinations or initiate specific treatments because none has proven its effectiveness in shortening this type of cough. On the other hand, when a cough persists beyond 8 weeks, the chance of spontaneous resolution decreases considerably. “This is when an assessment is necessary to identify a possible underlying cause,” Guilleminault noted.

“The absence of coughing during the consultation should not lead to ruling out a diagnosis,” he added.

Neurological Link

A large-scale French study of 70,000 patients examined the demographic profiles of patients with COVID-19. It revealed a lower frequency of coughing among children and older individuals, with a notable prevalence among adults aged 30-60 years.

Furthermore, during the acute phase of COVID, coughing did not appear to indicate severity. A comparison between survivors and nonsurvivors revealed no significant differences in the frequency and severity of coughing. Another study concluded that, contrary to expectations, COVID-related pneumonia, although potentially severe, does not necessarily involve severe cough.

These findings highlight the absence of a direct link between coughing and pulmonary involvement in patients with COVID-19.

“Coughing appears to be more closely linked to neurological dysfunction than to classic respiratory involvement. A distinction that is essential for better understanding the pathophysiology of the disease and guiding therapeutic strategies,” Guilleminault noted.

Cough Mechanism

“The analysis of cough in the context of phylogenetic evolution is fascinating,” explained Guilleminault. “It illustrates how this reflex has provided an advantage to the virus for its propagation.” Studies on the transmission of SARS-CoV-2 have confirmed that coughing plays a key role in the spread of viral particles. However, this mechanism does not involve severe pulmonary damage. The primary goal of the virus is to induce neurological dysfunction in the host by triggering a cough reflex. This neurological activation enables the virus to trigger a cough reflex for dissemination even without significant pulmonary damage. This mechanism provides an evolutionary advantage by enhancing the ability of the virus to spread and colonize new hosts.

The cough mechanism remains partially understood and involves cough hypersensitivity, characterized by increased neural responsivity to a range of stimuli that affect the airways, lungs, and other tissues innervated by common nerve supplies. The cough reflex begins with the activation of sensitive peripheral receptors located mainly in the respiratory tract that detect irritants or abnormalities.

These receptors, such as P2X2, P2X3, and others, transmit information to the brainstem, which coordinates the reflex response. This process is modulated by cortical controls that normally inhibit spontaneous coughing, explaining why we do not cough constantly even in the presence of moderate stimuli.

However, when there is an imbalance in this inhibition mechanism, coughing can be triggered either excessively or uncontrollably. SARS-CoV-2 appears to interact directly with these peripheral receptors, stimulating the cough reflex. The widespread presence and density of these receptors make this mechanism highly effective for the virus’s transmission.

Additionally, the vagus nerve likely plays a central role in triggering cough, particularly in viral infections. Studies of influenza have shown the involvement of sensory cells associated with the vagus nerve.

The virus stimulates the vagus nerve, which activates the cough reflex. Research suggests that neurotropism, neuroinflammation, and neuroimmunomodulation via the vagal sensory nerves, which are involved in SARS-CoV-2 infection, lead to cough hypersensitivity.

One question remains: Could vagus nerve involvement prolong coughing beyond the active phase of viral infection? The data indicate that viral infection significantly increases the sensitivity of the cough reflex, regardless of the level of irritation. The brain areas involved in inhibiting this reflex appear less effective during viral infection, resulting in reduced inhibitory control and easier triggering of cough. This phenomenon reflects temporary dysfunction of the neurological modulation system, which gradually recovers after recovery.

Long-Term Effects

The epidemiology of post-COVID cough and its integration into the framework of the long COVID framework remain subjects of ongoing debate. Early studies have revealed that cough could be either an isolated symptom or associated with other manifestations of long COVID. These studies were often conducted over relatively short periods (14-110 days) and estimated that approximately 19% of patients with long COVID experienced persistent cough. Another study found that 14% of patients reported cough between 3 weeks and 3 months after hospital discharge for COVID-19.

Longer follow-up periods showed a significant decrease in the prevalence of cough over time. For instance, a 1-year study reported that only 2.5% of patients had episodes of chronic cough.

However, a 2023 study published in JAMA found that the prevalence of post-COVID chronic cough exceeded 30% in some groups of patients.

“It is not relevant to wait so long before acting,” Guilleminault said. A reasonable threshold for evaluation and treatment is 8-12 weeks postinfection to begin investigations and consider appropriate treatment. What should be done when a patient presents with “Doctor, I had COVID, I have a cough, and it hasn’t stopped?” These situations are common in clinical practice. In terms of severity, quality of life, and overall impact, patients with chronic post-COVID cough are not significantly different from those with other chronic coughs. Moreover, both conditions involve a real neurological dysfunction.

Same Diagnostic Steps

Management should follow existing guidelines, including the recent French recommendations for chronic cough.

A visual analog scale can be used, and possible complications should be assessed. A chest x-ray is recommended to identify any warning signs, such as cough, although linked to COVID — may coincide with other conditions, such as bronchial cancer. In smokers, chest CT should be considered to rule out neoplastic pathology. The presence of interstitial lesions, particularly fibrosing lesions, suggests that fibrosing interstitial pneumonia requires specialized management.

Smoking, which is an aggravating factor, should be discontinued. Discontinuing angiotensin-converting enzyme inhibitors for 4 weeks can help determine if they contribute to cough.

The three most common causes of chronic cough — rhinosinusitis, asthma, and gastroesophageal reflux disease — should be ruled out. Diagnosis is based on history, physical examination, and specific tests: Nasofibroscopy for rhinosinusitis, spirometry, fractional exhaled nitric oxide for asthma and clinical history of gastroesophageal reflux disease. Studies have indicated that asthma may develop after a COVID infection.

Laryngeal abnormalities are also common in chronic post-COVID cough. One study found that a quarter of patients had increased laryngeal sensitivity or voice changes. “The larynx, a highly cough-producing organ, causes more coughing than the lungs,” Guilleminault explained.

Laryngeal abnormalities are frequently observed. A study found that 63% of patients experienced dysphonia, 56% had a sensation of a foreign body in the larynx, and 10% experienced laryngospasms.

These issues are common in patients with post-COVID cough and are often associated with neurological dysfunction. Innervation of the larynx is complex and can be affected by viruses, leading to hypersensitivity, paresthesia, and other sensory disturbances, which may explain the laryngeal symptoms observed in these patients.

Next Steps

If common causes such as asthma, abnormal imaging findings, or laryngeal pathology are ruled out, the condition may be classified as a chronic refractory or unexplained cough. In these cases, the neurological origin is likely due to nervous system dysfunction. Neuromodulatory treatments including amitriptyline, pregabalin, and gabapentin may be considered in some cases. Corticosteroids are generally ineffective against chronic coughs.

This story was translated fromMedscape’s French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.